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char = f;code = 102
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char = s;code = 115
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char = o;code = 111
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char = s;code = 115
char = t;code = 116
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char = t;code = 116
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char = ;code = 32
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char = e;code = 101
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char = d;code = 100
char = o;code = 111
char = c;code = 99
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char = n;code = 110
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = r;code = 114
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = -;code = 45
char = (;code = 40
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char = e;code = 101
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char = h;code = 104
char = y;code = 121
char = l;code = 108
char = h;code = 104
char = e;code = 101
char = x;code = 120
char = y;code = 121
char = l;code = 108
char = );code = 41
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = N;code = 78
char = S;code = 83
char = L;code = 76
char = 3;code = 51
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = L;code = 76
char = e;code = 101
char = y;code = 121
char = d;code = 100
char = i;code = 105
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells.
Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells.
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char = u;code = 117
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char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = N;code = 78
char = S;code = 83
char = L;code = 76
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
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char = p;code = 112
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char = d;code = 100
char = e;code = 101
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char = r;code = 114
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char = d;code = 100
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char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = e;code = 101
char = s;code = 115
char = t;code = 116
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char = c;code = 99
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char = a;code = 97
char = r;code = 114
char = ;code = 32
char = L;code = 76
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char = l;code = 108
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char = g;code = 103
char = h;code = 104
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char = d;code = 100
char = ;code = 32
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char = o;code = 111
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char = t;code = 116
char = a;code = 97
char = l;code = 108
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char = l;code = 108
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char = a;code = 97
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char = d;code = 100
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char = u;code = 117
char = t;code = 116
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = l;code = 108
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char = a;code = 97
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char = .;code = 46
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char = r;code = 114
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char = l;code = 108
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char = e;code = 101
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char = L;code = 76
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char = l;code = 108
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char = ;code = 32
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = f;code = 102
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char = c;code = 99
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char = D;code = 68
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char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
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char = s;code = 115
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char = o;code = 111
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char = f;code = 102
char = e;code = 101
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char = ;code = 32
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char = o;code = 111
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char = a;code = 97
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char = p;code = 112
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char = t;code = 116
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char = t;code = 116
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char = s;code = 115
char = t;code = 116
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char = t;code = 116
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char = o;code = 111
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char = e;code = 101
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char = e;code = 101
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char = t;code = 116
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char = t;code = 116
char = h;code = 104
char = ;code = 32
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char = t;code = 116
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char = n;code = 110
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char = o;code = 111
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char = ;code = 32
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char = c;code = 99
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char = t;code = 116
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = 3;code = 51
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = 3;code = 51
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = /;code = 47
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
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char = n;code = 110
char = e;code = 101
char = w;code = 119
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = 3;code = 51
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = L;code = 76
char = e;code = 101
char = y;code = 121
char = d;code = 100
char = i;code = 105
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Insulin-like 3 (INSL3) is a small peptide produced by testicular Leydig cells throughout embryonic and postnatal life and by theca and luteal cells of the adult ovary. During fetal life, INSL3 regulates testicular descent in males, whereas in adults, it acts as an antiapoptotic factor for germ cells in males and as a follicle selection and survival factor in females. Despite its considerable roles in the reproductive system, the mechanisms that regulate Insl3 expression remain poorly understood. There is accumulating evidence suggesting that androgens might regulate Insl3 expression in Leydig cells, but transcriptional data are still lacking. We now report that testosterone does increase Insl3 mRNA levels in a Leydig cell line and primary Leydig cells. We also show that testosterone activates the activity of the Insl3 promoter from different species. In addition, the testosterone-stimulating effects on Insl3 mRNA levels and promoter activity require the androgen receptor. We have mapped the testosterone-responsive element to the proximal Insl3 promoter region. This region, however, lacks a consensus androgen response element, suggesting an indirect mechanism of action. Finally we show that mono-(2-ethylhexyl) phthalate, a widely distributed endocrine disruptor with antiandrogenic activity previously shown to inhibit Insl3 expression in vivo, represses Insl3 transcription, at least in part, by antagonizing testosterone/androgen receptor action. All together our data provide important new insights into the regulation of Insl3 transcription in Leydig cells and the mode of action of phthalates.

Publication: Endocrinology 2008 Sep ;149(9)::4688-94. :doi: 10.1210/en.2008-0310.
Publication Date: 2008 Sep
Study Author(s): Laguë, Eric;Tremblay, Jacques J;
Institution: Department of Reproduction, Perinatal, and Child Health, Centre Hospitalier Universitaire of Québec Research Centre, CHUL Room T1-49, 2705 Laurier Boulevard, Québec City, Québec, Canada G1V 4G2.
Shortcut link to this study:
Insulin-like 3 (INSL3) is a small peptide produced by testicular Leydig cells throughout embryonic and postnatal life and by theca and luteal cells of the adult ovary. During fetal life, INSL3 regulates testicular descent in males, whereas in adults, it acts as an antiapoptotic factor for germ cells in males and as a follicle selection and survival factor in females. Despite its considerable roles in the reproductive system, the mechanisms that regulate Insl3 expression remain poorly understood. There is accumulating evidence suggesting that androgens might regulate Insl3 expression in Leydig cells, but transcriptional data are still lacking. We now report that testosterone does increase Insl3 mRNA levels in a Leydig cell line and primary Leydig cells. We also show that testosterone activates the activity of the Insl3 promoter from different species. In addition, the testosterone-stimulating effects on Insl3 mRNA levels and promoter activity require the androgen receptor. We have mapped the testosterone-responsive element to the proximal Insl3 promoter region. This region, however, lacks a consensus androgen response element, suggesting an indirect mechanism of action. Finally we show that mono-(2-ethylhexyl) phthalate, a widely distributed endocrine disruptor with antiandrogenic activity previously shown to inhibit Insl3 expression in vivo, represses Insl3 transcription, at least in part, by antagonizing testosterone/androgen receptor action. All together our data provide important new insights into the regulation of Insl3 transcription in Leydig cells and the mode of action of phthalates.
PMID: 18499751

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